Dexlansoprazole, also known as 2-(R)-[(3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methyl)sulfinyl]-1H-benzimidazole, is an enantiomer of lansoprazole. Dexlansoprazole is a proton pump inhibitor and is used in the treatment of pathologies such as erosive esophagitis, gastro-oesophageal reflux disease and gastro-intestinal disorders.
Dexlansoprazole has been disclosed in WO 92/08716 and solid crystalline forms are described in U.S. Pat. No. 6,462,058. U.S. Pat. No. 6,462,058 exemplifies a crystalline anhydrous form (with a melting point of 147-148° C.) and a sesquihydrate form (with a melting point of 76-80° C.).
Crystalline anhydrous Dexlansoprazole, as described in U.S. Pat. No. 7,285,668, has a higher thermal stability than other solid forms of dexlansoprazole. U.S. Pat. No. 7,285,668 also includes processes for obtaining the anhydrous crystalline form by crystallization from C1-C4 alkyl acetate and wherein the compound is dissolved at a concentration of between approximately 0.1 and 0.5 mg/mL. This method for the preparation of crystalline anhydrous dexlansoprazole has a limited industrial applicability, because during said process a significant degradation of the starting products occurs and the yields of crystalline anhydrous dexlansoprazole are low.
U.S. Pat. No. 8,314,241 describes a process for the preparation of crystalline anhydrous dexlansoprazole comprising the dispersion of dexlansoprazole in an alcoholic solvent, its complete dissolution by heating the dispersion of dexlansoprazole at temperatures not higher than 40° C., and the subsequent cooling of the solution to obtain the precipitation of dexlansoprazole in anhydrous crystalline form and the recovery of the solid.
The inventors of the present invention, which are partly the same inventors of U.S. Pat. No. 8,314,241, have surprisingly found a new process for the preparation of crystalline anhydrous dexlansoprazole that differs from the method described in U.S. Pat. No. 8,314,241 and does not include the step of complete dissolution of dexlansoprazole in an alcoholic solvent and the addition of an anti-solvent to precipitate the product. This new method allows for obtaining crystalline anhydrous dexlansoprazole without the formation or increase of degradation products. Furthermore, said crystals have the following advantageous properties: they have a better filterability, they can be more easily formulated, are free of colored impurities, and the crystals are more stable at higher temperatures than those obtained by the method described in U.S. Pat. No. 8,314,241.